Accepted Manuscript Title: Simultaneous determination of 40 novel psychoactive stimulants in urine by liquid chromatography-high resolution mass spectrometry and library matching Author: Marta Concheiro Marisol Castaneto Robert Kronstrand Marilyn A. Huestis PII: DOI: Reference:
S0021-9673(15)00527-0 http://dx.doi.org/doi:10.1016/j.chroma.2015.04.002 CHROMA 356421
To appear in:
Journal of Chromatography A
Received date: Revised date: Accepted date:
30-11-2014 30-3-2015 1-4-2015
Please cite this article as: M. Concheiro, M. Castaneto, R. Kronstrand, M.A. Huestis, Simultaneous determination of 40 novel psychoactive stimulants in urine by liquid chromatography-high resolution mass spectrometry and library matching, Journal of Chromatography A (2015), http://dx.doi.org/10.1016/j.chroma.2015.04.002 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Simultaneous novel psychoactive substances (NPS) analysis is highly challenging.
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NPS constantly emerge with similar or completely new chemical structures.
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The method quantifies 40 urinary NPS and 4 metabolites by LC-HRMS.
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Screening and confirmation data acquired in full scan and data dependent MS2.
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100 µL urine volume achieved 2.5-5 µg/L limit of quantification (LOQ).
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Simultaneous determination of 40 novel psychoactive stimulants in urine by
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liquid chromatography-high resolution mass spectrometry and library matching
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Chemistry and Drug Metabolism, Intramural Research Program, National Institute on
Drug Abuse, National Institutes of Health, Baltimore, MD, USA
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Currently Department of Sciences, John Jay College of Criminal Justice, City University
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Marta Concheiro1,2, Marisol Castaneto1,3, Robert Kronstrand4, Marilyn A. Huestis1*
of New York, New York, NY, USA 3
Program in Toxicology, University of Maryland Baltimore, Baltimore, MD, USA
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Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic
Medicine, Linköping, Sweden Division of Drug Research, Department of Medical and
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Health Sciences, Linköping University, Linköping, Sweden
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Corresponding author
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Professor Dr. Dr. (h.c.) Marilyn A. Huestis
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Chief, Chemistry and Drug Metabolism
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Biomedical Research Center (BRC)
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National Institute on Drug Abuse, NIH
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251 Bayview Blvd, Suite 200 Room 05A721
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Baltimore, MD 21224
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email:
[email protected] 28
Phone: 443-740-2524
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Fax: 443-740-2823
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Abstract
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The emergence of novel psychoactive substances is an ongoing challenge for analytical
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toxicologists. Different analogs are continuously introduced in the market to circumvent
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legislation and to enhance their pharmacological activity. Although detection of drugs in
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blood indicates recent exposure and link intoxication to the causative agent, urine is still
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the most preferred testing matrix in clinical and forensic settings. We developed a
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method for the simultaneous quantification of 8 piperazines, 4 designer amphetamines
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and 28 synthetic cathinones and 4 metabolites, in urine by liquid chromatography
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coupled to high-resolution mass spectrometry (LC-HRMS). Data were acquired in full
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scan and data dependent MS2 mode. Compounds were quantified by precursor ion
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exact mass, and confirmed by product ion spectra library matching, taking into account
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product ions’ exact mass and intensities. One-hundred µL urine was subjected to solid
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phase cation exchange extraction (SOLA SCX). The chromatographic reverse-phase
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separation was achieved with gradient mobile phase of 0.1% formic acid in water and in
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acetonitrile in 20 min. The assay was linear from 2.5 or 5 to 500µg/L. Imprecision (n=15)
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was